Prospective, Single-Center, Open-Label, Pilot Study Using Cryopreserved Umbilical Tissue Containing Viable Cells in the Treatment of Complex Acute and Chronic Wounds

Robert F. Mullins, MD; Zaheed Hassan, MD; Bounthavy Homsombath, MD; Shawn Fagan, MD; Beretta Craft-Coffman, PA-C; Joan Wilson, MSN, MHA, RN; John G. Rumbaugh, MD; Molly Saunders, BS; Alla Danilkovitch, PhD

Disclosures

Wounds. 2020;32(8):221-227. 

In This Article

Discussion

The purpose of the present study was to prospectively evaluate the clinical outcomes of vCUT plus standard of care (SOC) in the treatment of acute and chronic complex wounds. A vCUT allograft is a commercially available cryopreserved umbilical cord tissue that retains the components and properties inherent to native tissue; however, outcomes of vCUT in a variety of indications have only been evaluated in smaller retrospective case studies.[10,12–14]

Generally, very little published data exist regarding effective treatment options for patients with complex wounds. Split-thickness skin grafts (STSGs) are one of the most commonly used procedural techniques when wounds cannot be closed by primary intention. The success of STSGs relies on a well-vascularized wound bed with healthy granulation tissue. Due to the lack of vascularity and paucity of sites with exposed bone, tendon, muscle, or hardware, STSGs are not always a feasible treatment option for complex wounds.[15]

To address this issue, complex wounds are often pre-treated with negative pressure wound therapy (NPWT). Negative pressure wound therapy is the process by which subatmospheric pressure is either continuously or intermittently applied to the wound through a specialized pump in a close sealed system. This therapy has been shown to promote granulation tissue and tissue perfusion, as well as decrease edema, bacterial colonization, and wound drainage.[16–19]

Argenta and Morykwas[20] first described prospective clinical outcomes with NPWT in the treatment of 300 acute and chronic wounds. A total of 296 wounds responded favorably to the NPWT treatment, though specific outcomes (eg, time to healing) were not reported. In 2000, DeFranzo et al[21] evaluated 75 patients with lower extremity complex wounds and found that NPWT decreased edema and, subsequently, the surface area of the wound. Additionally, these wounds presented with healthy granulation tissue and bacterial counts that had significantly decreased. Of the 75 patients, 71 achieved wound closure, with 12 wounds treated by delayed primary closure, 58 with an STSG, and 5 with a flap.[21] Overall, the literature supports the use of NPWT in the treatment of nonhealing wounds; however, there is limited data from larger, prospective studies that show efficacy in the treatment of complex wounds without the need for additional adjunctive therapy.[22]

In recent years, skin substitute use for difficult-to-heal wounds has become more prevalent in wound care facilities. One such product, BMWD, a bilayered skin replacement system comprised of a porous matrix of cross-linked bovine tendon collagen and glycosaminoglycan and a semi-permeable silicone layer, has been on the market since 2004 (INTEGRA Bilayer Wound Matrix; Integra LifeSciences).[23]

Iorio et al[8] performed a retrospective review on the use of BMWD application for lower extremity limb salvage. Patients were classified as either high risk for amputation or low risk for amputation and then further separated into cohorts with and without diabetes for analysis. In low-risk patients with diabetes, 17% progressed to amputation, and 54% of high-risk patients with diabetes progressed to amputation.[8] In low-risk patients without diabetes, only 3% progressed to amputation. This study[8] showed positive clinical outcomes for the use of BMWD in the population of low-risk patients without diabetes. The rate of salvage was not improved for high-risk patients with diabetes. Further, patients had to undergo at least 2 surgical procedures. Once revascularization was achieved after intraoperative BMWD application, patients returned to the operating room to receive a skin graft. No closure rates were reported.[8]

Another skin substitute that has been used in the treatment of complex wounds is cryopreserved placental membrane containing viable cells (vCPM). In 2016, Frykberg et al[24] described the clinical outcomes of a weekly application of cryopreserved human placental membrane plus SOC in the treatment of chronic complex DFUs. After 16 weeks of treatment, 96.3% of patients achieved 100% granulation, and 59.3% of patients achieved complete wound closure in an average of 9.1 weeks.[24] Also in 2016, a clinical effectiveness review[25] was conducted for 12 patients who were treated with a weekly application of vCPM plus SOC in the management of complex wounds. All 12 wounds achieved complete wound closure without adjunct interventions such as NPWT, hyperbaric oxygen, or surgery in an average time of 10 weeks.[25]

Similar to vCPM, vCUT retains the components and anti-inflammatory, antimicrobial, anti-fibrotic, and angiogenic properties inherent to fresh placental tissue.[26–29] As such, it was hypothesized that positive clinical outcomes also would be seen utilizing vCUT in the treatment of complex wounds. In the current study, the proportion of patients that achieved 100% granulation was 80%, and 30% of wounds went on to achieve complete closure by the end of the 4-week treatment period.

In the 2 representative cases, the first patient was able to achieve complete closure of all 3 wounds. Although the second patient did not achieve closure, the patient had a significant reduction in wound size and 100% granulation in only 4 weeks. Closure in 4 weeks would not necessarily be expected in this patient population with larger, complex wounds.

The main difference between vCUT and other advanced therapies that have been used to treat complex wounds is that these therapies often require additional surgical procedures or therapies after granulation to achieve closure. This is often the case with BMWD usage specifically, as STSGs are often used in conjunction with BMWD after a wound granulates. In these instances, the silicone layer of the BMWD graft needs to be removed, along with any excessive granulation, necrotic tissue, and areas of incomplete take.[23] Following this, an epidermal autograft needs to be harvested and attached to the wound site. This can be problematic, as not every patient is a good candidate for an autograft, and an additional wound donor site is created. Patients with significant comorbidities, such as diabetes and peripheral vascular disease, can have impaired reepithelialization of the initial wound site and donor site.[30]

A vCUT allograft has the added benefit of not requiring any additional surgical steps, though surgery can be considered if needed. Wound closure is achievable without the use of an autologous graft or other adjunctive therapy in the outpatient setting. This was demonstrated in the previously mentioned 10-patient retrospective case series involving complex wounds with gas gangrene.[10]

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